Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

Objective To explore the characteristic categories of presenteeism among ICU nurses and analyse the influencing factor.Methods A convenience sampling method was adopted to select 391 ICU nurses as the study subjects from four Grade IIIA hospitals in Zhejiang Province in May 2023.A general information questionnaire,the Stanford presenteeism scale-6,and Maslach burnout inventor were used in the survey.R language was used for latent profile analysis,and univariate analysis and multinomial logistic regression analysis were employed to explore the influencing factors of the latent profiles.Results A total of 391 ICU nurses completed the survey,with the score of presenteeism at 16.10±4.64,which was at medium level.The score of presenteeism was further divided into four latent classes:low work limitation-low work energy type accounted for 13.04%,high work limitation-moderate work energy type accounted for 24.55%,low work limitation-high work energy type accounted for 4.86%,moderate work limitation-moderate work energy type accounted for 57.55%.The influencing factors include average monthly income,the score of emotional exhaustion and personal fulfillment dimensions in job burnout(all P<0.05).Conclusion The incidence of presenteeism among the ICU nurses has distinctive classification characteristics.Based on the identified influencing factors,nursing managers should provide individualised interventions to the ICU nurses with different latent profiles of characteristic categories to reduce the presenteeism among the nurses and thereby to improve the quality of nursing services.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

Objective:To investigate the prevalence and independent risk factors of non-alcoholic fatty liver disease (NAFLD) and advanced chronic liver disease among the type 2 diabetes mellitus (T2DM) population in the Shenyang community, so as to provide evidence for the prevention and control of T2DM combined with NAFLD.Methods:This cross-sectional study was conducted in July 2021. 644 T2DM cases from 13 communities in Heping District, Shenyang City were selected. All the surveyed subjects underwent physical examination (measurements of height, body mass index, neck circumference, waist circumference, abdominal circumference, hip circumference, and blood pressure), infection screening (excluding hepatitis B and C, AIDS, and syphilis), random fingertip blood glucose, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). The study subjects were divided into the non-advanced chronic liver disease group and the advanced chronic liver disease group according to whether the LSM value was greater than 10 kPa. Cirrhotic portal hypertension development was indicated in patients with LSM ≥ 15 kPa. The comparison of multiple mean values among the sample groups was performed by analysis of variance when the normal distribution was met.Results:In the T2DM community population, there were 401 cases (62.27%) combined with NAFLD, 63 cases (9.78%) combined with advanced chronic liver disease, and 14 cases (2.17%) combined with portal hypertension. There were 581 cases in the non-advanced chronic liver disease group and 63 cases (9.78%) in the advanced chronic liver disease group (LSM ≥10 kPa), including 49 cases (7.61%) with 10 kPa≤LSM<15 kPa, 11 cases (1.71%) with 15 kPa ≤LSM<25 kPa, and 3 cases (0.47%) with LSM ≥ 25 kPa. Age, body mass, body mass index, neck circumference, waist circumference, hip circumference, waist-to-height ratio, systolic blood pressure, and CAP were all statistically different between the non-advanced chronic liver disease group and the advanced chronic liver disease group ( F=-1.983,-2.598,-4.091,-2.062,-3.909, -4.581,-4.295,-2.474, and -5.191, respectively; P<0.05). There was a statistically significant difference in terms of whether or not there was combined cerebrovascular disease (2=4.632, P=0.031); however, there were no statistically significant differences in terms of lifestyle, diabetes complications, and other complications ( P>0.05). Conclusion:Patients with T2DM have a higher prevalence of NAFLD (62.27%) than those with advanced chronic liver disease (9.78%). 2.17% of T2DM cases in the community may not have had early diagnosis and early intervention, and they might have been combined with cirrhotic portal hypertension. So, the management of these patients should be strengthened.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective To explore the effect of Dexmedetomidine (Dex) on acute brain edema in mice in condition with targeted temperature management (TTM) following traumatic brain injury (TBI).Methods A total of 180 male C57BL/6J mice were divided into control group,sham operation group,TBI group,TBI + Dex group,TBI + TTM group,and TBI + Dex + TTM group according to the random number table (n =30 per group).The sham operation group only opened the bone window but did not hit it,and the control group did not open the bone window.The TBI + Dex,TBI + TIM,and TBI + Dex + TTM groups were intraperitoneally injected with Dex (60 μg/kg once every 2 h for 3 times) and/or hypothermia after TBI.The brain tissue injury volume,EB extravasation and brain water content of each group were determined by toluidine blue,Evans blue staining and dry-wet weight method at 24 hours after injury.Real-time quantitative PCR and Western blot were used to detect the expression of Claudin-5 in the injured brain tissue.At 24,48,and 72 hours after injury,the neurological deficiency degree was assessed using the modified neurological severity scores (mNSS).Results Compared with the sham operation group,TBI mice showed significant increase in brain tissue injury volume [(0.49 ± 0.04)mm3 vs.(1 1.57 ± 1.01)mm3],blood-brain barrier permeability [(16.4 ± 0.8) μg/g vs.(54.3 ± 1.7) μg/g],brain tissue water content [(76.7 ± 0.9) ％ vs.(83.1 ± 0.8) ％],and mNSS score [(1.6 ± 0.7) points vs.(13.4 ± 0.7) points] at 24 hour after TBI (all P ＜ 0.01).However,Dex or TTM treatment reduced brain tissue injury volume [(7.20±0.18)mm3 and (5.94 ±0.18)mm3],blood-brain barrier permeability [(32.7 ± 1.2) μg/g and (27.6 ± 1.0) μg,/g],brain tissue water content [(78.5 ± 0.4) ％ and (78.2 ± 0.6) ％],and neurological function [mNSS:(7.3 ± 1.1) points and (5.8 ± 1.3) points] (all P＜0.01).Moreover,Dex + TTM group showed better neuroprotection [reduced brain tissue injury volume:(3.92 ± 0.05) mm3,reduced BBB permeability:(21.6 ± 0.7) μg/g,reduced brain water content:(77.7 ±0.3)％,and reduced mNSS:(4.3 ± 1.2) points] compared with Dex or TTM alone (all P ＜ 0.01).Additionally,the mRNA expression of Claudin-5 (0.23 ± 0.01) decreased significantly at 24 hours after TBI compared with sham group (0.93 ± 0.04,P ＜ 0.01),but Dex or TTM could increase the expression of Claudin-5 (0.47 ± 0.01,and 0.54 ± 0.09) compared with TBI group (P ＜0.01),especially that of TBI + Dex + TTM group (0.64 ± 0.02,P ＜ 0.01).Furthermore,the protein expression of Claudin-5 was in accordance with the result of its mRNA expression.Conclusion Dex in condition with targeted temperature management can up-regulate Claudin-5 expression in early TBI,protect the integrity of blood-brain barrier,attenuate acute brain edema and neurological damage,and improve neurological function recovery.

Objective To evaluate the value of MR DWI combined with dynamic contras-t enhanced (DCE)scanning in the differential diagnosis of orbital lymphoma and inflammatory pseudotumor.Methods The clinical and imaging data of 1 5 cases with orbital lymphoma and 10 cases with inflammatory pseudotumor confirmed by surgery and pathology were analyzed retrospectively.25 patients were performed with conventional MR scanning,DWI scanning and DCE scanning.ADW4.7 software was used for DWI images and DCE images pos-t processing for analyzing the two groups of lesions in the TIC subtyping.Independent sample t test statistical analysis was used for comparing two groups of ADC values and Tmax values.The ROC curve was used for determining the statistically significant differences in measurement data of the threshold.With pathologic and immunohistochemical results as the gold standard,the accuracy,sensitivity and specificity of DWI combined with DCE in the diagnosis of orbital lymphoma and inflammatory pseudotumor were further detected.Results Among the 1 5 patients with orbital lymphoma,8 cases (8/15)occurred in the lacrimal gland area,5 cases (5/1 5)occurred in the outer cone space and 2 cases (2/15)occurred in the eyelid.Among the 10 patients with inflammatory pseudotumor,6 cases (6/10)occurred in the lacrimal gland and 4 cases (4/10)in the bulb.Among the 25 patients,9 of them had the TIC curve of outflow,6 of them had the TIC curve of platform and 10 of them had the TIC curve of inflow.The ADC value of orbital lymphoma was (0.573 ±0.1 1 6)×10－3 mm2/s,and the Tmax value was (248.2±1 59.4)ms.The ADC value of inflammatory pseudotumor was (1.186±0.244)×10－3 mm2/s,and the Tmax value was (5 5 7.6 ±98.7)ms.With the ADC＝0.885×10－3 mm2/s for the threshold,the AUC was 0.9 3 6 ,with diagnostic accuracy of 9 1.3%, the sensitivity of 90.1% and specificity of 80%.With the Tmax＝481.2 ms as the threshold,the AUC was 0.927,with the diagnosis accuracy rate of 88%,the sensitivity of 80%,and the specificity of 86.7%. Finally,DWI combined with DCE could reach the AUC 0.945, diagnostic accuracy of 89.5%,sensitivity of 93.3%,and specificity of 82.6%.Conclusion Conventional MRI scan combining DWI with DCE could show the histological components of the lesion of orbital tumor,which is of certain significance for the qualitative diagnosis of orbital lymphoma and inflammatory pseudotumor.